Lymphogranuloma venereum pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nate Michalak, B.A.
Overview
Lymphogranuloma venereum (LGV) is caused by serovars L1, L2, or L3 of the bacterium Chlamydia trachomatis. C. trachomatis is an obligate intracellular pathogen transmitted through vaginal, anal, or oral sexual contact. C. trachomatis alternates between two forms: the infectious elementary body (EB) and noninfectious, replicating reticulate body (RB). EBs enter through skin abrasions or microabrasion, or by crossing mucous membranes. EBs produce major out membrane protein (MOMP), which binds to heparan sulfate receptors on epithelial cells and are then phagocytized forming chlamydial inclusions. EBs begin to differentiate into RBs that start replicating. Endocytosis and bacterial replication cause host cell destruction leading to the formation of a papule at the site of inoculation. EBs and RBs then travel through lymphatics to regional lymph nodes, primarily to inguinal lymph nodes. C. trachomatis continues to replicate within monocytes causing lymphadenopathy and eventually the formation of buboes. Associated conditions include coinfection with other sexually transmitted diseases.
Pathophysiology
Transmission
- Lymphogranuloma venereum (LGV) may develop after transmission of servars L1, L2, or L3 of the bacterium Chlamydia trachomatis.
- C. trachomatis can be transmitted through vaginal, anal, or oral sexual contact.[1]
- C. trachomatis is an obligate intracellular pathogen.[2]
Pathogenesis
- Inoculation and replication of C. trachomatis serovars L1, L2, or L3 depends on alternation between two forms of the bacterium: the infectious elementary body (EB) and noninfectious, replicating reticulate body (RB).[3]
- The EB form is responsible for inoculation with C. trachomatis.
- The C. trachomatis EB enters the body through skin abrasions, microabrasions incurred during sexual intercourse or by crossing epithelial cells of mucous membranes.[4]
- C. trachomatis produces the extracellular ligand major outer membrane protein (MOMP), which is presumed to bind with heparan sulfate host epithelial cells.[3]
- Once bound, the EB is engulfed by receptor-mediated endocytosis creating vacuoles termed "inclusions".[5]
- EB inclusions are able to avoid lysosomal fusion, thus preventing their destruction.
- Once inside the host cell, EBs immediately start differentiating into reticulate bodies (RBs) that undergo replication.
- The process of endocytosis and accumulation of RBs within host epithelial cells causes host cell destruction (necrosis) which leads to the formation of a papule at the site of inoculation which may ulcerate, depending on the extent of infection and number or EBs transmitted.[5]
- After necrosis, EBs and RBs travel via lymphatics to regional lymph nodes, primarily to inguinal lymph nodes.
- Systemic infection occurs when this process repeats as C. trachomatis is phagocytized by and continues to replicate in monocytes, causing lymphadenopathy and eventually the formation of inguinal buboes.[1]
Virulence Factors
- C. trachomatis produces major outer membrane protein (MOMP), which is responsible for attachment of C. trachomatis EBs to mucous membrane epithelial cells
- Functional MOMP is required for C. trachomatis infection.[6]
Adhesion
- MOMP is 40 kDa ligand composed of 4 symmetrically spaced variable domains (VDs) I to IV.
- VD II and IV have been identified as the domains responsible for attachment:[6]
- VD II structure promotes electrostatic interactions
- VD IV structure promotes hydrophobic interactions
Associated Conditions
Coinfection with other sexually transmitted diseases including:
References
- ↑ 1.0 1.1 Ceovic R, Gulin SJ (2015). "Lymphogranuloma venereum: diagnostic and treatment challenges". Infect Drug Resist. 8: 39–47. doi:10.2147/IDR.S57540. PMC 4381887. PMID 25870512.
- ↑ Datta B, Njau F, Thalmann J, Haller H, Wagner AD (2014). "Differential infection outcome of Chlamydia trachomatis in human blood monocytes and monocyte-derived dendritic cells". BMC Microbiol. 14: 209. doi:10.1186/s12866-014-0209-3. PMC 4236547. PMID 25123797.
- ↑ 3.0 3.1 Taraktchoglou M, Pacey AA, Turnbull JE, Eley A (2001). "Infectivity of Chlamydia trachomatis serovar LGV but not E is dependent on host cell heparan sulfate". Infect Immun. 69 (2): 968–76. doi:10.1128/IAI.69.2.968-976.2001. PMC 97976. PMID 11159992.
- ↑ Mabey D, Peeling RW (2002). "Lymphogranuloma venereum". Sex Transm Infect. 78 (2): 90–2. PMC 1744436. PMID 12081191.
- ↑ 5.0 5.1 Moulder JW (1991). "Interaction of chlamydiae and host cells in vitro". Microbiol Rev. 55 (1): 143–90. PMC 372804. PMID 2030670.
- ↑ 6.0 6.1 Su H, Watkins NG, Zhang YX, Caldwell HD (1990). "Chlamydia trachomatis-host cell interactions: role of the chlamydial major outer membrane protein as an adhesin". Infect Immun. 58 (4): 1017–25. PMC 258576. PMID 2318528.